The major focus of this project is to explore the therapeutic efficacy of specific immunotoxins (IT) used either alone or in conjunction with chemotherapy via an intracavitary approach against tumors confined to the peritoneal cavities of athymic mice. Two models under investigation are a human colon (Ht-29) and ovarian (OVCAR-3) carcinoma xenografted intraperitoneally (ip) in nude mice. Studies have revealed that following ip inoculation of either Ht.29 or OVCAR-3 a localized disease is presented which is characterized by malignant ascites and solid tumor throughout the peritoneal cavities of mice. Drug studies involving Ht-29 revealed that the administration of 300 mg/kg of cytoxan in combination with 100 mg/kg of WR-2721, at 10 and 17 days, post-tumor cell inoculation resulted in a significant increase (P=.002) in MST (61 days) as compared to a MST of 35 days in the controls. Likewise, the ip injection of 200 mg/kg of cytoxan and 5 mg/kg of cis- platinum to mice bearing OVCAR-3 disease resulted in an increase in survival time, with a range of death 90 to 120 days as compared to a death range of 40 to 50 days in the control group. Mice that received either three or six injections of the IT, OVB-3 (PE), .5 mu g, every other day beginning 3 days post-tumor inoculation (3 million), exhibited increased MSTs (P=.002) of 62 and 68 days, respectively, as compared to a MST of 33 days for the controls. OVB-3 alone was ineffective. Nr-Lu-10 (PE) given ip at a similar dose and regimen to mice bearing the colonic disease showed similar MST's of 50 and 60 days, respectively, (P=.002). Groups of mice that received two, four or seven treatments of OVB-3 (PE) following cytoxan therapy, at a time of minimal tumor burden, exhibited a further significant increase (P less than or equal to .002) in MST's to 81, 89, and 96 days, respectively, compared to a MST of 59 in the drug treated group. Similarly, multiple treatments of Nr-Lu-lO (PE) following debulking therapy gave MSTs of 89, 97, and 105 days, respectively (P less than or equal to .002). Finally, OVB-3 (PE) is being tested against OVCAR-3 following cytoxan and cis-platinum therapy.